In current cancer (malignant tumor) treatment, surgery, irradiation or chemotherapy is used alone or in any combination thereof as required. Among them, anti-cancer agents (anti-malignant-tumor agents) used in the chemotherapy inherently have cytotoxicity or cell inhibition and damage not only the cancer (malignant tumor) cells but also human normal cells to cause side effects. Thus, it is important that the anti-cancer agents are administered to patients so as to prevent or reduce such side effects as far as possible and to provide sufficient anti-cancer (anti-malignant-tumor) effects.
Examples of the side effects caused by the administration of anti-cancer agents include blood disorders, gastrointestinal disorders and nerve disorders, and, in particular, acute or chronic nerve disorders have increased as a recent trend. This trend is considered to be caused by the following factors: frequent occurrence of nerve disorders as a main side effect of new anti-cancer agents providing remarkable anti-cancer effects, the effects of multiple drug therapy as recent main therapy, and an improving tendency of side effects such as blood disorders and gastrointestinal disorders. In this manner, no effective countermeasures against the nerve disorders, which are a main side effect caused by the current cancer chemotherapy, are available once the disorders have developed, due to the difficulty of nerve cell regeneration. Therefore, serious symptoms or irreversible disorders may be caused because of the difficulty of nerve cell regeneration. Accordingly, the nerve disorders that are the main side effect are an important therapeutic problem.
The nerve disorders caused by the administration of anti-cancer agents are observed in, besides the central nervous system, the autonomic nervous system, and the peripheral nervous system, the sense organs such as the sense of taste. Among them, nerve disorders that occur in a comparatively high frequency to be problems are pains such as a stinging pain and burning pain, paresthesia such as numbness of limb extremities and a burning sensation, hyperesthesia such as hypersensitivity to cold stimuli, dysesthesia such as sensory loss, sensory paralysis and sense of discomfort, and nerve disorders in the peripheral nervous system such as sensory ataxia and muscle weakness. The lesions in the peripheral nervous system induced by the administration of anti-cancer agents are considered mainly due to axonal degeneration. Microtubules in the axon play an important role in maintaining the normal function of cells, for example, forming a spindle during cell division, placing the subcellular organelle and transporting substances. Taxane drugs such as paclitaxel and docetaxel and vinca alkaloid drugs such as vincristine, vinblastine, vindesine and vinorelbine target the microtubules to inhibit the proliferation of malignant tumor cells. Thus, it is considered that the microtubules in normal nerve cells are also damaged to cause the nerve disorders. Furthermore, it is considered that platinum drugs such as oxaliplatin, carboplatin, cisplatin and nedaplatin directly damage nerve cells and consequently axonopathy is secondarily caused.
However, the neurotoxicity of the anti-cancer agents has not been studied in detail and preventive and supportive methods for the nerve disorders have yet to be established. Therefore, for relieving numbness symptoms, vitamin preparations such as mecobalamin and a Chinese herbal medicine, Gosha-jinki-gan, are used. For pains, an antidepressant (amitriptyline hydrochloride), an antiepileptic agent (carbamazepine), an antiarrhythmic agent (mexiletine hydrochloride), adrenocorticosteroid and the like are used. However, the radical treatment or prophylaxis has yet to be established. Accordingly, stopping/reducing the administration of a medicinal agent is the only reliable method for preventing the development of the nerve disorders (however, even after stopping the administration, the nerve disorders may continue or get worse). In view of the above problems, prophylactic or alleviating agents effective against a nerve disorder induced by anti-cancer agents have been strongly required in clinical practices.
The extract from inflamed tissues inoculated with vaccinia virus as an active ingredient in the medicinal agent of the present invention is disclosed to have the following effects: an analgesic effect, sedative effect, anti-stress effect and anti-allergic effect (see Patent Document 1); an immunostimulating effect, anti-cancer effect and cirrhosis inhibitory effect (see Patent Document 2); a treatment effect against idiopathic thrombocytopenic purpura (see Patent Document 3); a treatment effect against postherpetic neuralgia, brain edema, dementia, spinocerebellar degeneration and the like (see Patent Document 4); a treatment effect against Raynaud syndrome, diabetic neuropathy, sequelae of subacute myelo-optico-neuropathy and the like (see Patent Document 5); a kallikrein production inhibitory effect and peripheral circulatory disorder improving effect (see Patent Document 6); a bone atrophy improving effect (see Patent Document 7); a nitric oxide production inhibitory effect effective for the treatment of sepsis and endotoxic shock (see Patent Document 8); a treatment effect against osteoporosis (see Patent Document 9); a treatment effect against AIDS based on a Nef action inhibitory effect and chemokine production inhibitory effect (Patent Documents 10 and 11); a treatment effect against ischemic disorders such as cerebral infarction (Patent Document 12); a treatment effect against fibromyalgia syndrome (Patent Document 13); and a treatment effect against infections (Patent Document 14) and the like.
In particular, Patent Document 5 describes that the extract from inflamed tissues inoculated with vaccinia virus as an active ingredient in the medicinal agent of the present invention improves symptoms such as numbness, pain, coldness of limbs and paresthesia that are caused by the dysfunction of ischemic tissues or organs due to local blood circulation disorders of living organisms. However, the improving effect on numbness, pain, coldness of limbs, paresthesia and the like by the extract from inflamed tissues inoculated with vaccinia virus disclosed in Patent Document 5 is an effect based on the bloodstream improving effect on an ischemic condition due to blood circulation disorders. By contrast, such a prevention or alleviation effect in the present invention on the peripheral nerve disorders as the side effect (cellular damage) induced by the administration of anti-cancer agents is the effect of the extract on the peripheral nerve disorders having entirely different developing mechanisms and is unknown findings. That is, it is not known that the extract is effective for, for example, alleviation of peripheral nerve disorders that are considered to be caused by the damage of microtubules of nerve axons, demyelination of nerve axons, direct damage to nerve cells and the like induced by the administration of anti-cancer agents, and such medical use has not been published and reported yet.
[Patent Document 1]
    Japanese Patent Application Publication No. JP-A-53-101515[Patent Document 2]    Japanese Patent Application Publication No. JP-A-55-87724 (pages 3, 5 and 6)[Patent Document 3]    Japanese Patent Application Publication No. JP-A-1-265028 (pages 1 and 2)[Patent Document 4]    Japanese Patent Application Publication No. JP-A-1-319422 (pages 3 and 4)[Patent Document 5]    Japanese Patent Application Publication No. JP-A-2-28119 (page 3)[Patent Document 6]    Japanese Patent Application Publication No. JP-A-7-97336 (page 4)[Patent Document 7]    Japanese Patent Application Publication No. JP-A-8-291077[Patent Document 8]    Japanese Patent Application Publication No. JP-A-10-194978[Patent Document 9]    Japanese Patent Application Publication No. JP-A-11-80005 (pages 2 and 3)[Patent Document 10]    Japanese Patent Application Publication No. JP-A-11-139977[Patent Document 11]    Japanese Patent Application Publication No. JP-A-2000-336034 (pages 2 and 3)[Patent Document 12]    Japanese Patent Application Publication No. JP-A-2000-16942[Patent Document 13]    International Publication No. WO 2004/039383[Patent Document 14]    Japanese Patent Application Publication No. JP-A-2004-300146